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Trial registered on ANZCTR


Registration number
ACTRN12617000468325
Ethics application status
Approved
Date submitted
22/03/2017
Date registered
31/03/2017
Date last updated
6/03/2019
Date data sharing statement initially provided
6/03/2019
Date results information initially provided
6/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Study determining whether treatment of elderly subjects with oral BEZ235 alone or in combination with RAD001 decrease the incidence of respiratory tract infections
Scientific title
A multicenter dose-finding study to determine if oral BEZ235 alone or in combination with RAD001 decreases the incidence of respiratory tract infections in elderly subjects
Secondary ID [1] 291546 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Respiratory Tract Infections 302528 0
Condition category
Condition code
Respiratory 302072 302072 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The study will be conducted in two parts.

PART 1
Eligible participants will be randomized to 1 of 3 treatment groups in a ratio of 1:1:1.
Group 1: oral BEZ235 5 mg capsules taken once daily for 16 weeks
Group 2: oral BEZ235 10 mg capsules daily taken once daily for 16 weeks
Group 3: oral Matched placebo capsules taken once daily for 16 weeks

PART 2
Group 1: Chosen oral BEZ235 capsule dose from Part 1 (dose showing greatest efficacy with good tolerability) taken once daily for 16 weeks
Group 2: oral BEZ235 10 mg capsule + oral RAD001 0.1 mg tablets taken once daily for 16 weeks
Group 3: oral Placebo capsule taken once daily for 16 weeks
Part 2 will be conducted in the Northern Hemisphere with a different set of participants.

all medications to be given to participants will be Adherence to the treatment will be monitored by reviewing patient diary entries and monitoring returned treatment bottles.

Intervention code [1] 297531 0
Prevention
Comparator / control treatment
Placebo will be used as the control and comparator for the study for both Part 1 and Part 2.

BEZ235 matching placebo will be presented in a hard gelatin capsule and has the same contents minus the active ingredient.
Control group
Placebo

Outcomes
Primary outcome [1] 301497 0
Determine the efficacy of 2 different doses of BEZ235 alone or in combination with RAD001 on the incidence of respiratory tract infection in elderly subjects. The outcome will be assessed by physicians using chest x-ray, blood tests, etc.
Timepoint [1] 301497 0
16 weeks from start of treatment
Secondary outcome [1] 332863 0
Assess the safety and tolerability of 2 different doses of BEZ235 alone or in combination with RAD001. This outcome will be assessed by following adverse event reports, safety labs (hematology and chemistry) and physical exams.
Timepoint [1] 332863 0
7 days post-dose (16 weeks treatment plus 7 days)
Secondary outcome [2] 332864 0
Evaluate the effect of BEZ235 alone or in combination with RAD001 compared to placebo on the incidence of respiratory tract infections (RTIs) for 24 weeks. The outcome will be assessed by physicians using using chest x-ray, blood tests, etc.
Timepoint [2] 332864 0
24 weeks from start of treatment
Secondary outcome [3] 332865 0
Evaluate the effect of BEZ235 alone or in combination with RAD001 compared to placebo on the incidence of laboratory-confirmed viral RTIs for 16 weeks as assessed by respiratory virus PCR of nasopharyngeal swabs
Timepoint [3] 332865 0
16 weeks from start of treatment
Secondary outcome [4] 332866 0
Evaluate the pharmacokinetics (PK) of 2 different doses of BEZ235 given alone or in combination with RAD001. PK parameters such as AUC, Tmax, T1/2 will be assessed. RAD concentrations will be measured in blood. BEZ concentrations will be measured in serum.
Timepoint [4] 332866 0
At week 4, 6 and 8 after start of treatment

Eligibility
Key inclusion criteria
1. Male and female subjects without unstable medical conditions as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening and
A. Age 85 years and above
or
B. Age 65 years and above with one or more of the following conditions:
a. Current smoker
b. COPD Gold Class I or II (post bronchodilator FEV1/FVC < 0.70 and FEV1 less than or equal to 50% predicted)
c. Asthma
d. Chronic bronchitis
e. CHF New York Heart Association functional classification I-II
f. T2DM
g. One or more emergency room visits or hospitalizations for a RTI during the previous 12 months
2. Females must be post-menopausal
3. Sexually active male subjects with a partner of child-bearing potential must be willing to wear a condom while on study drug and for 1 week after stopping study drug, and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
4. At screening and baseline, vital signs (systolic and diastolic blood pressure, pulse rate and respiratory rate) will be assessed in a sitting position after the subject has rested for at least three (3) minutes. Sitting vital signs should be within the following ranges:
a. oral body temperature between 35.0-37.5 degrees Celsius
b. systolic blood pressure, 90-160 mm Hg
c. diastolic blood pressure, 50-95 mm Hg
d. pulse rate, 40 - 95 bpm
5. Subjects must weigh at least 40 kg
Minimum age
65 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of myocardial infarction, coronary bypass surgery, or any percutaneous coronary intervention (PCI) within 6 months prior to Screening
2. New York Heart Association functional classification III-IV congestive heart failure
3. Subjects with Type I diabetes mellitus
4. Subjects with clinically significant underlying pulmonary disease other than asthma, GOLD Class I and II COPD or chronic bronchitis
5. Subjects with a history of a systemic autoimmune disease or receiving immunosuppressive therapy including prednisone > 10 mg po daily
6. Any history of coagulopathy or medical condition requiring long-term anti-coagulation (low-dose aspirin treatment or equivalent is allowed)

The protocol has the full list of exclusion criteria

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation via phone/fax/email
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomization will be stratified into:
1. Age 85 years and above
2. Age 65 years and above with:
a. COPD
b. Asthma
c. Chronic bronchitis
d. T2DM
e. CHF
f. Current smoker
g. One or more emergency room visits or hospitalizations for a respiratory tract infection during the previous 12 months

Randomisation and sequence generation will be done via a computer system.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Data from two previous clinical trials conducted by Novartis (CRAD002X2202 and CBEZ235Y2201) suggests that 6 weeks of treatment of elderly participants 65 years of age and above with low doses of BEZ235 and/or RAD001 was safe and decreased the incidence of RTIs. The risk/benefit of BEZ235 alone or in combination with RAD001 may be most favorable in elderly subjects who are at increased risk of RTI-related morbidity and mortality. Therefore in the current study, elderly participants who are considered at increased risk of RTI-related morbidity and mortality will be enrolled.

The null hypothesis is that TRUE underlying proportion of patients with at least one RTI ocurrence is equal in all treatment arms. The alternative hypothesis is that at least one of the active treatment arms has TRUE underlying proportion of patients with at least one RTI ocurrence greater than that of placebo. The hypotheses will be assessed as described in the protocol.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 8747 0
New Zealand
State/province [1] 8747 0

Funding & Sponsors
Funding source category [1] 295940 0
Commercial sector/Industry
Name [1] 295940 0
resTORbio Inc.
Address [1] 295940 0
501 Boylston Street, Suite 6102, Boston, MA 02116, United States
Country [1] 295940 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
resTORbio Inc.
Address
501 Boylston Street, Suite 6102, Boston, MA 02116, United States
Country
United States of America
Secondary sponsor category [1] 294834 0
None
Name [1] 294834 0
Address [1] 294834 0
Country [1] 294834 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297221 0
Health and Disability Ethics Committee
Ethics committee address [1] 297221 0
Ministry of Health
133 Molesworth Street
Thorndon
Wellington 6011
Ethics committee country [1] 297221 0
New Zealand
Date submitted for ethics approval [1] 297221 0
23/03/2017
Approval date [1] 297221 0
05/05/2017
Ethics approval number [1] 297221 0

Summary
Brief summary
The purpose of this study is to evaluate the efficacy, tolerability and safety of BEZ235 alone or in combination with RAD001 in reducing the incidence of RTIs in elderly subjects at increased risk of RTI-related morbidity or mortality.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 73374 0
Dr Dean Quinn
Address 73374 0
P3 Research Limited
Level 1, 121 Adelaide Road, Mount Cook, Wellington 6021
Country 73374 0
New Zealand
Phone 73374 0
+64 4 801 0002
Fax 73374 0
Email 73374 0
dean@p3research.co.nz
Contact person for public queries
Name 73375 0
Mrs Elaine Gent
Address 73375 0
Pharmaceutical Solutions
Level 1, The Levy Building,
20 Customs Street East,
Auckland 1010
Country 73375 0
New Zealand
Phone 73375 0
+6493798205
Fax 73375 0
Email 73375 0
elaineg@pharmasols.com
Contact person for scientific queries
Name 73376 0
Mrs Elaine Gent
Address 73376 0
Pharmaceutical Solutions
Level 1, The Levy Building,
20 Customs Street East,
Auckland 1010
Country 73376 0
New Zealand
Phone 73376 0
+6493798205
Fax 73376 0
Email 73376 0
elaineg@pharmasols.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary